Emetine myopathy in the rat.

Area of Science:

• Pharmacology
• Toxicology
• Muscle Physiology

Background:

• Emetine, an alkaloid, is known for its emetic and amoebicidal properties.
• Potential toxic effects of emetine on skeletal muscle warrant investigation.
• Understanding the mechanism of emetine-induced myopathy is crucial for clinical management.

Purpose of the Study:

• To investigate the dose-dependent effects of emetine on rat skeletal muscle.
• To elucidate the cellular and subcellular mechanisms underlying emetine myopathy.
• To determine the role of denervation in emetine-induced muscle weakness.

Main Methods:

• Administration of varying doses of (-) emetine (0.25-2.0 mg/kg i.p.) to rats for up to 220 days.
• Assessment of physiological changes, including weight gain, muscle wet weight, and in vitro muscle strength.
• Histopathological examination of muscle fibers, including assessment of fiber types, necrosis, and enzyme activity (myofibrillar ATPase, NADH-TR).

Main Results:

• Low emetine doses (≤1.0 mg/kg) caused minimal physiological changes and focal enzyme loss in Type II and III fibers.
• High emetine dose (2.0 mg/kg) led to significant weight loss, severe muscle atrophy (20% reduction), and muscle weakness.
• Extensive structural damage, including necrotic and split fibers, and widespread enzyme loss in all fiber types were observed at the high dose.
• No evidence of functional or structural denervation was found.

Conclusions:

• Emetine-induced muscular weakness in rats is a direct myopathy affecting muscle fibers at a subcellular level.
• The observed myopathy is dose-dependent, with higher doses causing severe structural damage and atrophy.
• Nerve integrity is not implicated in the etiology of emetine myopathy.